title: Involvement of HIF-2α-mediated inflammation in arsenite-induced transformation of human bronchial epithelial cells.
abstract: Arsenic is a well established human carcinogen that causes diseases of the lung. Some studies have suggested a link between inflammation and lung cancer; however, it is unknown if arsenite-induced inflammation causally contributes to arsenite-caused malignant transformation of cells. In this study, we investigated the molecular mechanisms underlying inflammation during neoplastic transformation induced in human bronchial epithelial (HBE) cells by chronic exposure to arsenite. The results showed that, on acute or chronic exposure to arsenite, HBE cells over-expressed the pro-inflammatory cytokines, interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1β (IL-1β). The data also indicated that HIF-2α was involved in arsenite-induced inflammation. Moreover, IL-6 and IL-8 were essential for the malignant progression of arsenite-transformed HBE cells. Thus, these experiments show that HIF-2α mediates arsenite-induced inflammation and that such inflammation is involved in arsenite-induced malignant transformation of HBE cells. The results provide a link between the inflammatory response and the acquisition of a malignant transformed phenotype by cells chronically exposed to arsenite and thus establish a previously unknown mechanism for arsenite-induced carcinogenesis.
authors.affiliation: Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu, PR China; The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xu
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.forename: Wenchao
authors.initials: W
authors.lastname: Xu
authors.forename: Fei
authors.initials: F
authors.lastname: Luo
authors.forename: Bairu
authors.initials: B
authors.lastname: Wang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Pang
authors.forename: Qizhan
authors.initials: Q
authors.lastname: Liu
mesh_terms: D018053:Arsenites / Q000633:toxicity*; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D001980:Bronchi / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D060888:Real-Time Polymerase Chain Reaction; D017670:Sodium Compounds / Q000633:toxicity*; D013997:Time Factors; D015854:Up-Regulation; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D018053:Arsenites; D051792:Basic Helix-Loop-Helix Proteins; D016207:Cytokines; D017670:Sodium Compounds; D000099162:Endothelial PAS Domain-Containing Protein 1; C017947:sodium arsenite
keywords: Arsenite; Carcinogenesis; Hypoxia inducible factor-2α (HIF-2α); Inflammation